Detection of Chronic Myeloid Leukemia

Chronic myeloid leukemia (CML) is a chronic myeloproliferative clonal disease of multipotential hematopoietic stem cells, mainly involving the myeloid cell lineage and usually associated with the reciprocal chromosomal translocation t(9 22)(q34 qll). Chronic myeloid leukemia begins with an initial relatively benign chronic phase, progressing to a final blast crisis and characterized by marked leukocytosis due to large number of mature and immature neoplastic cells. 

The t(9 22)(q34 qll) translocation with its cytogenetic appearance as Philadelphia chromosome was the first demonstrated chromosome rearrangement in neoplasia. This translocation is the hallmark of the chronic myeloid leukemia nevertheless it is also found in association with other hematological malignancies such as acute 

It is worth mentioning that the BCR-ABL translocation is only a co-factor and not the direct cause of CML as this translocation may be detected at very low frequency in the blood ofhealthy individuals, which indicates that the BCR-ABLtranslocation is not the only genetic abnormality required for a malignant transformation. Furthermore, malignant cells harboring the t(9 22) translocation have an increased susceptibility to additional genetic mutations that induce tumor 

Chronic myeloid leukemia lacking the t(9 22) translocation is a known variant of CM L. About 5% of CML is associated with other cytogenetic abnormalities or seems to have a kind of link with a BCR-ABL gene located on one morphologically normallooking chromosome (either 22 or 9). The translocation t(5 12)(q33 pl3) andt(8 13) 

The amplification of BCR-ABL mRNA can be used for the diagnosis and monitoring of CML in addition to other hematological malignancies bearing this translocation. It is also a useful assay for the detection of minimal residual leukemia cells after bone marrow transplantation or specific therapy (so-called molecular relapse). Clinical observations demonstrate that a molecular relapse detected within the first sbc months after bone marrow transplantation is assodated with a high risk of disease relapse (in about 45% of cases), whereas a molecular relapse after a long period is less evident. 

---